title: Isoflurane on brain inflammation.
abstract: Brain inflammation may play an important role in the pathophysiology of early brain injury after subarachnoid hemorrhage (SAH). Our aim was to demonstrate brain inflammation development and to determine whether isoflurane, a clinically available volatile anesthetic agent, prevents brain inflammation after SAH. This study used 162 8-week-old male CD-1 mice. We induced SAH with endovascular perforation in mice and randomly assigned animals to sham-operated (n=21), SAH+vehicle-air (n=35) and SAH+2% isoflurane (n=31). In addition to the evaluation of brain injury (neurological scores, brain edema and Evans blue dye extravasation), brain inflammation was evaluated by means of expression changes in markers of inflammatory cells (ionized calcium binding adaptor molecule-1, myeloperoxidase), cytokines (tumor necrosis factor [TNF]-α, interleukin-1β), adhesion molecules (intercellular adhesion molecule [ICAM]-1, P-selectin), inducers of inflammation (cyclooxygenase-2, phosphorylated c-Jun N-terminal kinase [p-JNK]) and endothelial cell activation (von Willebrand factor) at 24h post-SAH. Sphingosine kinase inhibitor (N, N-dimethylsphingosine [DMS]) and sphingosine-1-phosphate receptor-1/3 antagonist (VPC23019) were used to block isoflurane's effects (n=22, each). SAH caused early brain injury, which was associated with inflammation so that all evaluated markers of inflammation were increased. Isoflurane significantly inhibited both brain injury (P<0.001, respectively) and inflammation (myeloperoxidase, P=0.022; interleukin-1β, P=0.002; TNF-α, P=0.015; P-selectin, P=0.010; ICAM-1, P=0.016; p-JNK, P<0.001; cyclooxygenase-2, P=0.003, respectively). This beneficial effect of isoflurane was abolished with DMS and VPC23019. Isoflurane may suppress post-SAH brain inflammation possibly via the sphingosine-related pathway.
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA.
authors.forename: Orhan
authors.initials: O
authors.lastname: Altay
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ostrowski
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, USA; Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, USA. Electronic address: johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007530:Isoflurane / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*
chemical_list: D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D007530:Isoflurane
keywords: BWC; Brain water content; COX-2; Cyclooxygenase-2; DMS; EBI; Early brain injury; ICAM-1; IL-1β; Inflammation; Intercellular adhesion molecule-1; Interleukin-1beta; Ionized calcium binding adaptor molecule-1; Isoflurane; MPO; Myeloperoxidase; N, N-dimethylsphingosine; Phosphorylated c-Jun N-terminal kinase; S1P; S1P1/3; SAH; SphK; Sphingosine 1-phosphate; Sphingosine kinase; Sphingosine-1-phosphate receptor-1/3; Subarachnoid hemorrhage; TNF-α; Tumor necrosis factor-alpha; iba-1; p-JNK; vWF; von Willebrand factor